Researchers Indicate That New Drug Shows Promise in Treating Mesothelioma

Mesothelioma cancer patients given pegargiminase had a 29% lower risk of death and 35% lower risk of disease progression in a recent clinical study.

Mesothelioma is a rare, but serious form of cancer associated with exposure to asbestos, which is often at a very advanced stage by the time it is diagnosed, resulting in a very short life expectancy after diagnosis. However, a new study suggests that patients may soon have access to a promising chemotherapy treatment, which could dramatically improve survival rates.

Researchers from the United Kingdom, the United States, Italy, and Australia indicate that pegargiminase (ADI-PEG 20) was successful in increasing overall survival among patients with advanced mesothelioma, especially those with the subtype nonepithelioid pleural mesothelioma. The findings were published on February 15 in the medical journal JAMA Oncology.

One of the few known causes of mesothelioma is exposure to asbestos fibers, which were used in a variety of manufacturing and building industries until most uses were banned in 1972. However, given the long latency period between last exposure and diagnosis, there continue to be new mesothelioma diagnoses each year, and the condition is nearly always fatal.

Pleural mesothelioma develops in the linings of the lungs. It has among the lowest long-term survival rate of any cancer that forms solid tumors, with only between 5% and 10% of patients surviving five years after diagnosis.

Certain cancers, including pleural mesothelioma, rely on the semi-essential amino acid arginine to survive, and respond to amino acid-depriving treatments. Pegargiminase (pegylated arginine deiminase) is a new drug that uses enzymes to target and deplete arginine, to stop cancer tumors from growing.

Pegargiminase Clinical Trial Study Shows Favorable Results

In the latest study, a team of international medical researchers conducted a clinical trial involving 249 patients diagnosed with nonepithelioid pleural mesothelioma, from 43 medical centers in five countries.

Study participants were first given pemetrexed and platinum chemotherapy treatments every three weeks for up to six cycles, and were then randomly assigned to receive weekly injections of either pegargiminase, or a placebo for 24 months or until the cancer progressed. A final-follow up was conducted a year after the study concluded to determine if the new drug was safe and successful in improving patient survival without cancer progression.

According to the data, 85 patients in the pegargiminase group and 84 patients in the placebo group stopped treatments due to disease progression. Five patients in the pegargiminase group died during treatment and 10 patients died in the placebo group. Twelve patients in the placebo group died from a fatal adverse event associated with treatment, compared to seven patients in the pegargiminase group.

In comparing survival rates after the 12-month follow up period, the data revealed a total of 105 participants in the pegargiminase group had died, compared to 116 participants in the placebo group. Those in the pegargiminase group had significantly longer survival overall, with an average of 9.3 months, compared to 7.7 months among those in the placebo group. The pegargiminase group also had a higher one-year survival rate of 41.4%, compared to 31.4% in the placebo group, according to the data.

Treatment May Have Dramatic Impact on Mesothelioma Survival Rates

The findings revealed those in the pegargiminase group had longer progression-free survival of an average 6.2 months, compared to an average 5.6 months in the placebo group. The overall response rate to treatment was 13.8% among those who received pegargiminase and 13.5% among those given a placebo. After 12 weeks of treatment, the overall response rate among the pegargiminase group was 85.1%, compared to 76.4% among the placebo group.

While the trial was initially supposed to be conducted as a three phase study, it was stopped after the second phase by the recommendation of the Data and Safety Monitoring Board (DSMB), after consulting with the U.S. Food and Drug Administration (FDA), and determining the drug showed positive and favorable results.

Researchers indicate the trial results are promising and pegargiminase may be key in treating mesothelioma cancer patients and keeping them alive longer. The findings warrant further research on using arginine-deleting drugs as a first-line chemotherapy option to treat nonepithelioid pleural mesothelioma cancer, they concluded.

Mesothelioma lawsuits are part of the largest mass-tort in U.S. history, with more than 600,000 people having filed a case against more than 6,000 defendants due to injuries caused by inhaling asbestos fibers. In addition to individuals directly exposed to asbestos, a number of the lawsuits filed in recent years have involved second-hand exposure among individuals who inhaled fibers carried on on the clothes or in the hair of their parents when they were children.